The present invention relates to methods of treating patients having chronic hepatitis C infection by administering a therapeutically effective induction amount of ribavirin and a therapeutically effective induction amount of pegylated interferon-alfa for a first treatment time period sufficient to substantially lower detectable HCV-RNA, followed by (2) administering a therapeutically effective amount of ribavirin and an therapeutically effective amount of pegylated interferon-alfa for a second treatment time period sufficient to eradicate detectable HCV-RNA at least by the end of the second treatment time period and to maintain no detectable HCV-RNA for at least 24 weeks after the end of the second treatment time period.
Chronic infection with hepatitis C virus is an insidious and slow-progressing disease having a significant impact on the quality of life. It can eventually result in cirrhosis of the liver, decompensated liver disease and/or hepatocelluar carcinoma.
International Publication No. WO98/48840 discloses use of pegylated interferon alfa to treat hepatitis C infections.
Nieforth et al. (Clin. Pharmacol. Ther., 1996, 59:636-646) has reported a comparison of the in vivo activity of Roferon(copyright)A and a polyethylene glycol-modified Roferon(copyright) A in healthy volunteers. The results, however, suggested that the conjugates could not be administered less than twice weekly and therefore offered little therapeutic advantage over the unmodified counterpart.
Co-pending, commonly assigned U.S. patent application Ser. No. 08/742,305 discloses methods of administering polymer-cytokine conjugates to individuals susceptible to treatment with the cytokine, but does not disclose the method of this invention.
Polyethylene glycol modification of other proteins has been reported by Fuertges et al. (Journal of Controlled Release,1990, Vol.11:139-48).
Combination therapy of interferon alfa-2b and ribavirin to treat chronic hepatitis C for 24 weeks is disclosed by Reichard et al. (Lancet 1998; 351;83-87)
T. Poynard et al. (Lancet, 1998, Vol. 352, 1426-1432) disclose that treating chronic hepatitis C patients who had not been treated with interferon or ribavirin with 3 MIU of interferon alfa-2b TIW plus 1000-1200 mg of ribavirin per day for 48 weeks resulted in a sustained virological response at 24 weeks after treatment in 43% of the patients. See also J. G. McHutchinson et al. (N. Engl. J. Med., 1998, 339:1485-1492), G. L. Davis et al. (N. Engl. J. Med. 339:1493-1499) disclose that treating chronic hepatitis C patients who relapsed after treatment with interferon with 3 MIU of interferon alfa 2b Tim plus 100-1200 mg of ribavirin per day for 48 weeks results in higher rates of sustained virologic response than treatment with interferon alone.
There is a need to provide an improved therapy for treating chronic hepatitis C patients to produce a sustained virological response at 24 weeks after treatment in a greater number of patients.
The present invention provides a method of treating patients having chronic hepatitis C infections which comprises (1) administering a therapeutically effective induction dosing amount of ribavirin and an therapeutically effective induction dosing amount of pegylated interferon-alfa for a first treatment time period sufficient to substantially lower detectable HCV-RNA, followed by (2) administering a therapeutically effective amount of ribavirin and an therapeutically effective amount of pegylated interferon-alfa for a second treatment time period sufficient to eradicate detectable HCV-RNA at least by the end of the second treatment time period and to maintain no detectable HCV-RNA for at least 24 weeks after the end of the second treatment time period.
The present invention also provides a method of treating patients having chronic hepatitis C infections which comprises (1) administering, in a first treatment time period of at least about four weeks, about 400-1200 mg per day of ribavirin and about 1.5 micrograms per kilogram of pegylated interferon-alfa-2b twice a week, followed by (2) administering, in a second treatment time period of up to about forty-four weeks, about 800-1200 mg per day of ribavirin and about 0.5 to 1.5 micrograms per kilogram of pegylated interferon-alfa-2b once a week.
The present invention also provides a method method of treating patients having chronic hepatitis C infections which comprises (1) administering, in a first treatment time period of from about four weeks up to about twelve weeks, about 400-1200 mg per day of ribavirin and about 1.5 micrograms/kilogram of pegylated interferon-alfa-2b twice a week followed by (2) administering, in a second time of from about thirty-six to about forty-four weeks, period about 800-1200 mg per day of ribavirin and about 0.5 to about 1.5 micrograms per kilogram of pegylated interferon-alfa-2b once a week basis.
The present invention also provides a method method of treating patients having chronic hepatitis C infections which comprises (1) administering, in a first treatment time period of about four weeks, about 800-1200 mg per day of ribavirin and about 1.5 micrograms/kilogram of pegylated interferon-alfa-2b twice a week, followed by (2) administering, in a second time of about forty-four weeks, about 800-1200 mg per day of ribavirin and about 1.5 micrograms/kilogram of pegylated interferon-alfa2b once a week